Martínez Vera Naira P, Schmidt Reinhold, Langer Klaus, Zlatev Iavor, Wronski Robert, Auer Ewald, Havas Daniel, Windisch Manfred, von Briesen Hagen, Wagner Sylvia, Stab Julia, Deutsch Motti, Pietrzik Claus, Fazekas Franz, Ropele Stefan
Department of Neurology, Medical University of Graz, Graz, Austria.
Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Muenster, Germany.
PLoS One. 2014 Mar 14;9(3):e92068. doi: 10.1371/journal.pone.0092068. eCollection 2014.
This study was performed to explore the feasibility of tracing nanoparticles for drug transport in the healthy rat brain with a clinical MRI scanner. Phantom studies were performed to assess the R1 ( = 1/T1) relaxivity of different magnetically labeled nanoparticle (MLNP) formulations that were based on biodegradable human serum albumin and that were labeled with magnetite of different size. In vivo MRI measurements in 26 rats were done at 3T to study the effect and dynamics of MLNP uptake in the rat brain and body. In the brain, MLNPs induced T1 changes were quantitatively assessed by T1 relaxation time mapping in vivo and compared to post-mortem results from fluorescence imaging. Following intravenous injection of MLNPs, a visible MLNP uptake was seen in the liver and spleen while no visual effect was seen in the brain. However a histogram analysis of T1 changes in the brain demonstrated global and diffuse presence of MLNPs. The magnitude of these T1 changes scaled with post-mortem fluorescence intensity. This study demonstrates the feasibility of tracking even small amounts of magnetite labeled NPs with a sensitive histogram technique in the brain of a living rodent.
本研究旨在探讨使用临床MRI扫描仪追踪纳米颗粒在健康大鼠脑中进行药物运输的可行性。进行了体模研究,以评估基于可生物降解人血清白蛋白且用不同尺寸磁铁矿标记的不同磁性标记纳米颗粒(MLNP)制剂的R1(=1/T1)弛豫率。在26只大鼠中进行了3T的体内MRI测量,以研究MLNP在大鼠脑和身体中的摄取效果及动力学。在脑中,通过体内T1弛豫时间映射对MLNP诱导的T1变化进行定量评估,并与荧光成像的死后结果进行比较。静脉注射MLNP后,在肝脏和脾脏中可见MLNP摄取,而在脑中未见视觉效果。然而,对脑中T1变化的直方图分析表明MLNP在整体上呈弥漫性存在。这些T1变化的幅度与死后荧光强度成比例。本研究证明了使用灵敏的直方图技术在活体啮齿动物脑中追踪即使少量磁铁矿标记的纳米颗粒的可行性。